DESCRIPTION: Debate exists regarding the relative role of various biomechanical factors (e.g., force, repetition, acceleration, etc.) during repetitive work in the causation of upper extremity musculoskeletal disorders. Most of these factors can be altered in the design of work. We will use our recently developed rabbit finger flexor model to investigate the role of these factors in causing entrapment neuropathy of the median nerve at the wrist and tendinosis at the epicondyle. In addition, the study will identify early cellular and biochemical changes in matrix proteins and cytokines. For 2 hours per day, 3 days per week for 10 weeks, the large finger flexor is repetitively stimulated while the fingertip load is controlled. The loading is performed under general anesthesia. The system allows for the precise control of repetition rate, peak fingertip force, load duration, and rate of loading. Three experiments will separately investigate the role of repetition rate, peak force, and loading rate on tissue function and structure. Work (integral of force over time) will be held constant across the loading conditions. Median nerve function is evaluated by measuring distal motor latency across the wrist, and morphologic differences in nerve fiber count, fiber density and myeination are quantified. Morphologic differences in the tendon attachment site at the epicondyle are evaluated with semi-quantitative and quantitative methods assessing cellularity, cell shape, collagen fiber linearity, neovascularization, edema, and apoptosis. The antigentic location and density of structural proteins (collagen I,II, ifi, decorin, tenascin, fibronectin), and various cytokines (IL- lb. TNF-a, TGF-B, bFGF, substance P) will be assessed using immunohistochemical methods. A fourth experiment will assess these biochemical endpoints at earlier times of exposure. This study has the potential to identify the characteristics of biomechanical loading, which are injurious; information valuable to occupational health practitioners in adding specificity to ergonomic guidelines for repetitive work. The study also has the potential to identify the biochemical pathways and time-frames of disease progression; information which may lead to new strategies for treating and preventing entrapment neuropathies and tendon disorders related to work.